All three branched-chain amino acids (leucine, isoleucine, and valine) figure prominently in the supplementation regimens of serious athletes due to their essential nature (they are not synthesized by the body and must be assimilated from dietary sources) and the roles they play in many key physiological functions. But one BCAA, leucine, has long been of special interest to medical researchers.
This is by virtue of leucine's unique capacity for facilitating muscle repair and growth, especially in the interval after high-intensity exercise has broken down existing muscle tissue. Indeed, leucine occupies a place at the very beginning of the chain reaction that results in new muscle mass.
Research has proven leucine to be a powerful muscle recovery activator, as it is primarily involved in protein synthesis. Specifically, leucine is a potent nutritive activator of muscle protein synthesis due to its ability to increase mRNA translation in muscle cells. Increased mRNA translation simply means an increase in the cell's efficiency to read the genetic material that manufactures amino acids and proteins. This occurs via leucine’s ability to directly stimulate mTOR complex 1 (a primary anabolic pathway). Unsurprisingly, lower blood levels of leucine have been associated in research with lower values of skeletal muscle index, strength and performance.
Leucine's beneficial effects aren't strictly limited to protein synthesis and recovery, either. Recent research suggests that leucine may support immune response by activating T cells along the same mTOR signaling pathway that regulates protein synthesis. Leucine has also been associated with supporting mitochondrial function, energy production (BCAAs can be used directly as fuel by the body), and glucose utilization. One particular avenue of research has generated exciting evidence that leucine supplementation may also offer unique wellness benefits to older people.
Leucine Linked to Reduced Age-Related Muscle Loss
One of the primary symptoms of aging is the gradual loss of muscle mass and functional strength. Researchers estimate that after the age of 30, we lose 3% to 5% of muscle mass per decade. Decreases in muscle mass directly correlate with increases in excess fat and decreases in work output capacity. Markers of optimal health, such as bone density, recovery from injury, and immune response are adversely affected as well.
Age-related muscle loss -- or sarcopenia -- can have a number of causes. Some are hormonal; some derive from lack of exercise and dietary deficiencies. There is also significant evidence that the cellular-level processes that govern muscle protein synthesis become less efficient as we age.
This last causative effect has led researchers to speculate that supplemental leucine may help older people retain muscle mass more effectively. Recent investigations into this theory are already generating some highly interesting results.
In a study just published in the Journal of Applied Physiology in May of 2021 , researchers sought to explore the connection between leucine availability and both insulin sensitivity and mitochondrial function associated with aging and muscular disuse. Older healthy adults were assigned a regimen of 7 days bed rest and 5 days inpatient rehabilitation, with some test subjects receiving supplemental leucine.
The researchers found that, during bed rest, leucine tended to preserve insulin sensitivity. Following rehabilitation, leucine increased ATP-linked respiration and preserved specific pathways of mitochondrial respiration, insulin sensitivity, and a marker of oxidative stress during bed rest and rehabilitation (1 Arentson-Lantz,et al).
In another clinical test conducted in Spain, researchers assessed the efficacy of leucine administration in improving muscle mass, muscle strength, functional performance and respiratory muscle function in institutionalized older individuals. The study was a placebo-controlled, randomized, double-blind design in fifty participants aged 65 and over randomized to a parallel group intervention of 13 weeks’ duration with a daily intake of leucine (6 g/day) or placebo (lactose, 6 g/day).
The researchers found that administration of leucine was well-tolerated and significantly improved some criteria of sarcopenia in elderly individuals such as functional performance measured by walking time and improved lean mass index. For respiratory muscle function, the leucine-treated group improved significantly in maximum static expiratory force compared to the placebo (2 Martínez-Arnau, et al).
In yet another study, published in 2018 in The American Journal of Clinical Nutrition, researchers measured the acute (hourly) and integrated (daily) myofibrillar protein synthesis (myoPS) response to consumption of a high-quality standard protein beverage compared with a high-quality protein beverage with added leucine.
Healthy older women aged 65–75 consumed a fixed, weight-maintaining diet and were randomly assigned to twice-daily consumption of either 15 g of a milk protein beverage containing 4.2 g leucine or 15 g of a mixed protein (milk and soy) beverage containing 1.3 g leucine. Unilateral leg resistance exercise allowed a determination of acute and integrated exercised and rested myoPS (protein synthesis) responses.
The researchers found that the 15-g protein-containing beverage with greater leucine content induced greater increases in acute and integrated myoPS (protein synthesis) than did the standard mixed-protein beverage. Declines in muscle mass in older women, they concluded "may be attenuated with habitual twice-daily consumption of a protein beverage providing protein and higher amounts of leucine." (3 Devries,et al)
Finally, in a study published in BMJ Open Sport & Exercise Medicine in 2017, researchers sought to evaluate the effect of a 12-week leucine-rich amino acid supplementation in combination with moderate training. In the study, 48 healthy subjects exercised for 30 minutes three times per week and received either a leucine-rich amino acid supplementation or a placebo. Before and after supplementation, subjects performed an exhaustive eccentric exercise protocol. Maximal concentric strength and safety assessments were performed before exercise and after 3, 24, 48 and 72 hours.
The researchers found that the supplementation with leucine resulted in reduced loss of strength at zero and 3 hours after downhill walking compared with the placebo. They concluded that the "principle findings show that leucine-rich amino acid supplementation can counteract the negative effects of eccentric exercise. The treatment resulted in a reduction of exercise-induced strength loss." (4 Reule CA, et al)
While more research is clearly warranted (especially among younger cohorts), leucine supplementation clearly can have a beneficial impact on the cellular protein synthesis that is the foundation of muscle recovery, retention and growth.
Since branched-chain amino acid content in muscle cells is known to decline precipitously during high-intensity exercise, it stands to reason that most, if not all, fitness conscious people can benefit from supporting EAA (essential amino acid) levels before, during, and after exercise.
1 Emily J. Arentson-Lantz, Jasmine Mikovic, Nisha Bhattarai,et al. Leucine augments specific skeletal muscle mitochondrial respiratory pathways during recovery following 7 days of physical inactivity in older adults. Journal of Applied Physiology, Vol. 130, No. 5, 11 May 2021.
2 Francisco M. Martínez-Arnau, Rosa Fonfría-Vivas, Cristina Buigues, Yolanda Castillo, Pilar Molina, Aldert J. Hoogland, Femke van Doesburg, Leo Pruimboom, Julio Fernández-Garrido and Omar Cauli. Effects of Leucine Administration in Sarcopenia: A Randomized and Placebo-controlled Clinical Trial. Nutrients 2020, 12(4), 932.
3 Michaela C Devries, Christopher McGlory, Douglas R Bolster, Alison Kamil, Maike Rahn, Laura Harkness, Steven K Baker, Stuart M Phillips. Protein leucine content is a determinant of shorter- and longer-term muscle protein synthetic responses at rest and following resistance exercise in healthy older women: a randomized, controlled trial. The American Journal of Clinical Nutrition, Volume 107, Issue 2, February 2018, Pages 217–226.
4 Reule CA, Scholz C, Schoen C, et al. Reduced muscular fatigue after a 12-week leucine-rich amino acid supplementation combined with moderate training in elderly: a randomised, placebo-controlled, double-blind trial. BMJ Open Sport & Exercise Medicine 2017.
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